The concentration, oxygenation, and flow characteristics of blood cells in the microvasculature profoundly affect nourishment and thermal regulation of surrounding tissues, abdnormal levels of these quantities will affect oxygen extraction and can potentially compromise surrounding tissue, ln-situ measurements of any one of these basic blood parameters provide insight about many physiological phenomena including cerebral metabolism and functional heterogeneity, internal bleeding, tumor vasculature, and ischemia. Measurement of more than one of these quantities simultaneously provides even deeper insight into fundamental tissue physiology, and offers the possibility to directly probe tissue oxygen metabolism. In this proposal we are concerned with measurement of these quantities in brain, ultimately human brain. Thus far a broad range of non-invasive techniques has been used to probe activity in the cerebral cortex. This proposal seeks to add a new technique to this arsenal. In particular we propose to construct and use a versatile multi-modality all-optical imaging probe for measurement of total hemoglobin concentration, blood oxygenation, blood flow, the cerebral metabolic rate for oxygen (CMRO2) and changes thereof in brain. The instrument is unusual in that it combines two qualitately different and complementary diffuse optical imaging modalities: (1) Diffuse Reflection Spectroscopy (DRS) for computation of blood oxygen saturation and total hemoglobin concentration, and (2) Diffuse Correlation Spectroscopy (DCS) for measurement ot blood flow. We anticipate this instrument and its variants will provide three-dimensional imaging of these properties in small animal brain, and will provide similar regional imaging information in human brain. The two diffuse optical imaging schemes are attractive new approaches for evaluating cerebral physiology. They can provide hemodynamic and metabolic imaging contrasts complementary to those of Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), and hold a unique potential for continous noninvasive bedside imaging in humans and densely sampled longitudinal studies in animals.